Yeast are commonly used for expression of heterologous proteins, and have several advantages as an expression system. Yeast are a simple and well-characterized eukaryotic organism, and yeast may be readily manipulated by present genetic engineering techniques.
Recent genetic engineering and fermentation efforts in yeast have been directed at methods to produce human proteins in useable form in yeast at commercially viable levels of production, and with a minimum of modification of the protein. Such efforts are described in, e.g., U.S. Pat. Nos. 4,775,622; 4,940,661; 5,010,003; 5,013,652; 5,922,569; 6,204,012; and 6,103,500.
Among other proteins, human alpha 1-antitrypsin (hAAT) has been cloned and produced in yeast. See, e.g., U.S. Pat. Nos. 4,752,576 and 4,839,283. However, it has heretofore been difficult to produce AAT in yeast in high concentrations in soluble form. Therefore, a need exists in the art for methods of producing proteins, such as soluble AAT, in yeast in high concentrations.